High sensitivity and amenability to miniaturization for field-portable applications have helped to make ion mobility spectrometry (IMS) an important technique for the detection of many compounds, including narcotics, explosives, and chemical warfare agents as described, for example, by G. Eiceman and Z. Karpas in their book entitled “Ion Mobility Spectrometry” (CRC, Boca Raton, 1994), the contents of which are incorporated herein by reference. In IMS, gas-phase ion mobilities are determined using a drift tube with a constant electric field. Ions are separated in the drift tube on the basis of differences in their drift velocities. At low electric field strength, for example 200 V/cm at approximately ambient atmospheric pressure, the drift velocity of an ion is proportional to the applied electric field strength, and the mobility, K, which is determined from experimentation, is independent of the applied electric field. Additionally, in IMS the ions travel through a bath gas that is at sufficiently high pressure that the ions rapidly reach constant velocity when driven by the force of an electric field that is constant both in time and location.
E. A. Mason and E. W. McDaniel in their book entitled “Transport Properties of Ions in Gases” (Wiley, N.Y. 1988), the contents of which are incorporated herein by reference, teach that at high electric field strength, for instance fields stronger than approximately 5,000 V/cm, the ion drift velocity is no longer directly proportional to the applied electric field, and K is better represented by KH, a non-constant high field mobility term. The dependence of KH on the applied electric field has been the basis for the development of high field asymmetric waveform ion mobility spectrometry (FAIMS). Ions are separated in FAIMS on the basis of a difference in the mobility of an ion at high field strength, KH, relative to the mobility of the ion at low field strength, K. In other words, the ions are separated due to the compound dependent behavior of KH as a function of the applied electric field strength.
In general, a device for separating ions according to the FAIMS principle has an analyzer region that is defined by a space between first and second spaced-apart electrodes. The first electrode is maintained at a selected dc voltage, often at ground potential, while the second electrode has an asymmetric waveform V(t) applied to it. The asymmetric waveform V(t) is composed of a repeating pattern including a high voltage component, VH, lasting for a short period of time tH and a lower voltage component, VL, of opposite polarity, lasting a longer period of time tL. The waveform is synthesized such that the integrated voltage-time product, and thus the field-time product, applied to the second electrode during each complete cycle of the waveform is zero, for instance VHtH+VLtL=0; for example +2000 V for 10 μs followed by −1000 V for 20 μs. The peak voltage during the shorter, high voltage portion of the waveform is called the “dispersion voltage” or DV, which is identically referred to as the applied asymmetric waveform voltage.
Generally, the ions that are to be separated are entrained in a stream of gas flowing through the FAIMS analyzer region, for example between a pair of horizontally oriented, spaced-apart electrodes. Accordingly, the net motion of an ion within the analyzer region is the sum of a horizontal x-axis component due to the stream of gas and a transverse y-axis component due to the applied electric field. During the high voltage portion of the waveform, an ion moves with a y-axis velocity component given by vH=KHEH, where EH is the applied field, and KH is the high field ion mobility under operating electric field, pressure and temperature conditions. The distance traveled by the ion during the high voltage portion of the waveform is given by dH=vHtH=KHEHtH, where tH is the time period of the applied high voltage. During the longer duration, opposite polarity, low voltage portion of the asymmetric waveform, the y-axis velocity component of the ion is vL=KEL, where K is the low field ion mobility under operating pressure and temperature conditions. The distance traveled is dL=vLtL=KELtL. Since the asymmetric waveform ensures that (VHtH)+(VLtL)=0, the field-time products EHtH and ELtL are equal in magnitude. Thus, if KH and K are identical, dH and dL are equal, and the ion is returned to its original position along the y-axis during the negative cycle of the waveform. If at EH the mobility KH>K, the ion experiences a net displacement from its original position relative to the y-axis. For example, if a positive ion travels farther during the positive portion of the waveform, for instance dH>dL, then the ion migrates away from the second electrode and eventually is neutralized at the first electrode.
In order to reverse the transverse drift of the positive ion in the above example, a constant negative dc voltage is applied to the second electrode. The difference between the dc voltage that is applied to the first electrode and the dc voltage that is applied to the second electrode is called the “compensation voltage” (CV). The CV prevents the ion from migrating toward either the second or the first electrode. If ions derived from two compounds respond differently to the applied high strength electric fields, the ratio of KH to K may be different for each compound. Consequently, the magnitude of the CV that is necessary to prevent the drift of the ion toward either electrode is also different for each compound. Thus, when a mixture including several species of ions, each with a unique KH/K ratio, is being analyzed by FAIMS, only one species of ion is selectively transmitted to a detector for a given combination of CV and DV. In one type of FAIMS experiment, the applied CV is scanned with time, for instance the CV is slowly ramped or optionally the CV is stepped from one voltage to a next voltage, and a resulting intensity of transmitted ions is measured. In this way a CV spectrum showing the total ion current as a function of CV, is obtained.
Numerous ionization sources, including atmospheric pressure ionization sources, have been described for use with FAIMS. Non-limiting examples include electrospray ionization and variants thereof, thermospray, atmospheric pressure chemical ionization, corona discharge, radioactive sources (including 63Ni and other nuclides). As some non-limiting examples, ions are detected using electrometers for measuring electric current from discharge of the ions, detected by measurement of currents induced by the presence of the ions, detected indirectly using chemical reactions, detected using optical methods such as laser scattering or optical fluoresence. In addition, detection of ions using a mass spectrometer is known.
A typical analytical system that includes FAIMS may include several devices operating in a cooperative manner. For example a sample may be prepared in automated fashion in a commercial robotic station, and transferred to an automatic sampling instrument. This autosampler provides portions of the sample to a separation device that includes gas chromatography or liquid chromatography or electrophoresis as some non-limiting examples of condensed or gas-phase separations. The compounds separated by this system may then be presented to an ionization device to convert the molecules of interest into their respective ions. This change of state of the analyte compound forms the junction between separations of molecules from separations of ions. The ions produced by this ionization system that may be one of electrospray ionization, optical ionization, MALDI ionization, corona discharge ionization, chemical ionization, and radioactive decay as some non-limiting examples, are then presented to a conventional ion mobility spectrometer or to FAIMS, or to a system composed of a hybridization of these methods. Previous disclosures have described some of these, including a tandem FAIMS-IMS system in WO 01/69221 published Sep. 20, 2001, the contents of which are incorporated herein by reference, and a tandem FAIMS-ion trapping system in U.S. Pat. No. 6,703,609, the contents of which are incorporated herein by reference. The FAIMS and drift ion mobility measurements may be made in tandem-in-space instruments or in tandem-in-time operations that may be within a single or a plurality of chambers designed for optimum performance of drift tube or FAIMS versions of high-pressure ion separation. The ions which have been separated by the drift tube, or FAIMS, or hybrid technology is then presented to one of a further separation, or a detection system. Several detection systems have been used including using electrometers for measuring electric current from discharge of the ions, measurement of currents induced by the presence of the ions, indirectly detected using chemical reactions, or detected using optical methods such as laser scattering or optical fluoresence as some non-limiting examples. If further separation is required, ions may be separated by mass spectrometers including one of quadrupole mass spectrometers, ion trap mass spectrometers, and Fourier Transform (FT) ion cyclotron mass spectrometers as some non-limiting examples.